In combinatorial chemistry, a large number of candidate materials are created from a relatively small set of precursors and subsequently evaluated for suitability for a particular application. As currently practiced, combinatorial chemistry permits scientists to systematically explore the influence of structural variations in candidates by dramatically accelerating the rates at which they are created and evaluated. Compared to traditional discovery methods, combinatorial methods sharply reduce the costs associated with preparing and screening each candidate.
Combinatorial chemistry has revolutionized the process of drug discovery. One can view drug discovery as a two-step process: acquiring candidate compounds through laboratory synthesis or through natural products collection, followed by evaluation or screening for efficacy. Pharmaceutical researchers have long used high-throughput screening (HTS) protocols to rapidly evaluate the therapeutic value of natural products and libraries of compounds synthesized and cataloged over many years. However, compared to HTS protocols, chemical synthesis has historically been a slow, arduous process. With the advent of combinatorial methods, scientists can now create large libraries of organic molecules at a pace on par with HTS protocols.
Recently, combinatorial approaches have been used for discovery programs unrelated to drugs. For example, some researchers have recognized that combinatorial strategies also offer promise for the discovery of inorganic compounds such as high-temperature superconductors, magnetoresistive materials, luminescent materials, and catalytic materials. See, for example, co-pending U.S. patent application Ser. No. 08/327,513 “The Combinatorial Synthesis of Novel Materials” (published as WO 96/11878) and co-pending U.S. patent application Ser. No. 08/898,715 “Combinatorial Synthesis and Analysis of Organometallic Compounds and Catalysts” (published, in part, as WO 98/03251), which are all herein incorporated by reference.
Because of the success of the combinatorial approach in eliminating the synthesis bottleneck in drug discovery, many researchers have come to narrowly view combinatorial methods as tools for creating structural diversity. Few researchers have emphasized that, during synthesis, variations in temperature, pressure, ionic strength, and other process conditions can strongly influence the properties of library members. For instance, reaction conditions are particularly important in formulation chemistry, where one combines a set of components under different reaction conditions or concentrations to determine their influence on product properties.
In recent years, researchers have begun to design apparatus to be used in combinatorial experiments that allow parallel processing of multiple reactions, particularly where it is desirable to vary one or more parameters of the reactions. For instance, commonly assigned pending U.S. application Ser. No. 09/548,848 filed on Apr. 13, 2000, discloses a parallel reactor including vessels for containing a plurality of reaction mixtures, a stirring system, and a temperature control system adapted to maintain the individual vessels or groups of vessels at different temperatures. The Ser. No. 09/548,848 application is a continuation-in-part of pending U.S. application Ser. Nos. 09/239,223 and 09/211,982 filed Jan. 29, 1999 and Dec. 14, 1998, respectively, wherein the Ser. No. 09/211,982 application is a continuation-in-part of pending U.S. Ser. No. 09/177,170 filed on Oct. 22, 1998, which is itself a continuation-in-part of Provisional Application No. 60/096,603 filed Aug. 13, 1998, now abandoned, all of which are incorporated herein by reference.
Commonly assigned pending Provisional Application Ser. No. 60/255,716 filed on Dec. 14, 2000, incorporated herein by reference, also describes a related apparatus. In particular application Ser. No. 60/255,716 discloses parallel semi-continuous or continuous reactors for synthesizing combinatorial libraries of materials and screening combinatorial libraries of materials such as catalysts.
Given the growing interest in combinatorial research, it may be desirable to have a parallel reactor adapted to create various flow paths through the reactor block while allowing in situ monitoring and control over the progress and properties of multiple parallel reactions, as well as permit the removal of a portion of the reaction mixtures during the experiment or the performance of flow-through experiments, wherein both sampling and flow-through can occur without depressurizing or reducing the pressure in the respective reaction chambers.